tbuckley/cabot-search huggingface dataset:
NeoPlus: A phase II study of neoadjuvant lenvatinib and pembrolizumab in resectable mucosal melanoma.
Authors: Lili Mao, Lu Si, Jie Dai, Xue Bai, Caili Li, Xiaoting Wei, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Bixia Tang, Bin Lian, Xuan Wang, Xieqiao Yan, Li Zhou, Yan Kong, Xiaowen Wu, Siming Li, Juan Li, Jun Guo
Journal: Journal of Clinical Oncology (2023)

9514 Background: Combination therapy of anti-PD1 agent with VEGFR inhibitor is a promising therapeutic approach in unresectable or metastatic mucosal melanoma. We conducted this study evaluating neoadjuvant lenvatinib and pembrolizumab in pts with resectable mucosal melanoma. Methods: This was a single-arm, open-label, single-center, ongoing phase 2 study conducted from Sep 2021. Eligible pts were adults (18-75 yr) with histologically confirmed, resectable mucosal melanoma. Pts received lenvatinib 20mg qd and pembrolizumab 200mg q3w for 2 cycles, followed by surgery. Pembrolizumab (200mg q3w) continued post operatively for further 15 cycles. The primary endpoint was complete pathologic response (pCR). Secondary endpoints were Event free survival (EFS), Overall survival (OS) and safety. Results: As of Dec 2022, 19 pts were enrolled with a median follow-up of 49 wks (95%CI, 38 -60). Median age was 57 yrs, 14 were female. Primary sites included: 8 female genital, 6 ano-rectal, 4 head &amp; neck (1 nasal, 3 oral),1 esophageal. 12 pts were localized disease,7(37%) were regional lymphatic disease. KIT or NRAS mutations were presented in 2 and 3 pts, respectively. 15 pts underwent surgery, 2 pts had a pCR (13.3 %), 1 MPR, 3 pPR, with a pathologic response rate of 40%(6/15,95%CI 16-67%). 4 pts did not proceed with planned surgery for pts preference. Median EFS has not been reached. IHC data of the resected tumor showed higher CD8+ T cells density in responders (R=pCR+ MPR + pPR) than non-responders (NR=pNR) (p = 0.04). In 6 pts(one pPR and 5pNR) with paired pre and post treatment samples, CD3+ and CD8+ T cells were significantly increased following treatment (p =0.03). Most common AEs were proteinuria (6, 32%), hypothyroidism (6, 32%), dysphonia (5, 26%). One pt(5%, 1/19) had grade 3 ALT elevation. No grade 4-5 toxicities were observed. Conclusions: The combination of pembrolizumab plus lenvatinib as neoadjuvant therapy in resectable MM is safe. The preliminary data has shown promising pathologic response with increased CD8+ T cell infiltration, supporting further investigation of neoadjuvant treatment in MM. Acknowledgement: Investigational funding and products are granted from Merck Sharp &amp; Dohme LLC. Clinical trial information: NCT04622566 .
Are we missing the beat in cancer end-of-life care: Prevalence and end-of-life monitoring of implantable cardioverter defibrillators in a population-based sample of older adults diagnosed with breast, colorectal, or pancreatic cancer.
Authors: Megan A Mullins, Kathryn Shahan, Vlad Zaha, Melanie Sulistio, Stephanie Terauchi, David E Gerber, Sandi Pruitt
Journal: Journal of Clinical Oncology (2023)

e18728 Background: More than 50,000 implantable cardioverter defibrillators (ICDs) are placed in adults aged 65 years and older in the United States each year to manage cardiac arrhythmias. Shared risk profiles between many cancers and heart disease, as well as cardiotoxic effects of anti-cancer treatments suggest individuals with cancer are likely to have ICD devices. Although ICDs have been studied extensively in Europe, little is known about the US population, and even less is known in populations with cancer. ICDs have critical implications for end-of-life care in patients with cancer. Many patients do not include wishes for their ICD in their advanced directives, and end-of-life shocks can cause pain and distress for patients and their families. We evaluated prevalence and end-of-life monitoring of ICDs in a national sample of older adults who had breast, colorectal, or pancreatic cancer. Methods: We analyzed Surveillance, Epidemiology and End Results (SEER) data for first incident breast, colorectal, and pancreas cancer cases linked to Medicare claims (years 2004-2016) in Medicare-beneficiaries aged ³66 years. We evaluated the prevalence of ICDs by cancer stage at diagnosis with descriptive statistics. For patients with late-stage cancer (III or IV) who died in our study period we also evaluated the prevalence of ICD monitoring at the end of life. Because ICD deactivation is not a billable code, we evaluated ICD monitoring as a proxy for having an active device, hence an opportunity to discuss device deactivation. Results: In our sample of 286,015 individuals with cancer, 6.8% of patients had evidence of an ICD in their Medicare claims (6.1% breast, 8.2% colorectal, 5.3% pancreas). Of these, 49.7% had evidence of an ICD before their cancer diagnosis. The prevalence of ICDs was lower among the 60,046 individuals diagnosed with late-stage cancer( p&lt; .001) (5.0% breast, 6.1% colorectal, 4.5% pancreas). Among individuals with late-stage cancer and evidence of an ICD, 27.0% of those who died had ICD monitoring in the last six months of life (21.1% breast, 27.9% colorectal, 29.3% pancreas, p= .001), and 6.2% had monitoring in the last month of life (5.1% breast, 6.5% colorectal, 6.3% pancreas, p= .46). Conclusions: To improve the quality of care at the end-of-life for people with advanced cancer, awareness, communication, and shared decision making about ICD device management options are important considerations. These data suggest there may be opportunities to discuss prognosis and implications of advanced-stage cancer at device monitoring visits or during cardio-oncology visits.
Prognostic value of baseline immune suppressive biomarkers to select non-small cell lung cancer (NSCLC) patients (pts) likely to benefit from the plinabulin/docetaxel (Plin/Doc) combination.
Authors: Trevor Feinstein, Gabrielle Legaspi, Stephen Duprez, Lan Huang, Ramon W. Mohanlal
Journal: Journal of Clinical Oncology (2023)

e21018 Background: Baseline Neutrophil-to-Lymphocyte (L) ratio (NLR), Platelet-to-L ratio (PLR), and L-to-Monocyte ratio (LMR) are biomarkers that can predict anticancer outcomes. Plin, a novel small molecule immune-enhancing agent, exerts anticancer activity by GEF-H1-dependent activation of dendritic cells, and hence T-cells. We evaluated the correlation of Plin’s anticancer effects with NLR, PLR, LMR immune suppressive (IS) signature. We correlated baseline NLR, PLR, and LMR (broken down in quartiles [Q]) with overall survival (OS) in NSCLC pts from the DUBLIN-3 trial, which had met the primary OS endpoint in favor of Plin/Doc vs Doc alone (Han ESMO 2021). Methods: DUBLIN-3 (NCT02504489) was a global Phase 3 study in 2 nd /3 rd line EGFR-wild type, stage IIIB/IV NSCLC pts (N = 559) randomized 1:1 to Plin/Doc or Doc alone. Doc (75 mg/m 2 on D1) and Plin (30 mg/m 2 on D1/D8) were given by IV infusions. Baseline (i.e., prior to dexamethasone premedication, Doc and Plin) blood draws were taken from each pt within 28 days prior to any study medication given to obtain baseline NLR, PLR, and LMR. The survival duration of each pt was obtained. NLR, PLR, and LMR values for Plin/Doc and Doc were divided into Qs, and the corresponding median OS for each Q was calculated. Only 2 nd line pts were included in this analysis to avoid confounding with multiple lines. Results: Increasing Qs of baseline NLR and PLR (thus with increasing IS signature) were associated with decreasing median OS for both Plin/Doc and Doc. Increasing Qs for LMR (thus with decreasing IS signature) were associated with increasing median OS in both Plin/Doc and Doc. Median OS in each Q was consistently higher with Plin/Doc vs Doc alone, except for Qs with an IS signature. With baseline NLR ≤3.6, PLR≤194, or LMR≥5.9, thus avoiding an IS signature, median OS was on average 2.5 Mo (range 0.6-4.5 Mo) longer with Plin/Doc vs Doc alone. For each of the Qs in the table, the n = 52 ± 2 pts. Conclusions: Baseline IS biomarkers were predictive of median OS with both Plin/Doc and Doc alone. Baseline NLR, PLR, and LMR, at cut-off levels to avoid IS levels, could serve as prognostic markers to identify likely responders to the immune-enhancing agent Plin in combination with Doc in NSCLC. Clinical trial information: NCT02504489 . [Table: see text]
Comparison of diversity across real-world evidence, randomized clinical trial, and Surveillance, Epidemiology, and End Results (SEER) data in patients with metastatic breast cancer.
Authors: Danielle Gentile, Alexandrina Balanean, Parisa Asgarisabet, Madison Brown, Richard Scott Swain, Andrew J. Klink, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2023)

e18670 Background: Compared with patients in typical care settings, participants in randomized clinical trials (RCTs) tend to be younger and less diverse. We compared representation of age, race, and ethnicity at initiation of first-line (1L) therapy for metastatic breast cancer across real-world evidence (RWE), RCT, and Surveillance, Epidemiology, and End Results (SEER) registry data. Methods: RWE and SEER inclusion criteria were based on corresponding RCTs. We compared age, race, and ethnicity at initiation of 1L therapy among female patients with metastatic breast cancer across 2 RWE chart review studies (completed between 2019-2021), 4 RCTs with similar eligibility (reported between 2014–2021), and the latest SEER registry data (2017–2019) using t-tests and 2-sided chi-square tests. Results: We collected demographics of 57,479 patients (RWE: n = 860, 1.5%; RCT: n = 2,707, 4.7%; SEER: n = 53,912, 93.8%). Mean age at 1L therapy initiation was significantly higher in RWE than RCT studies (61.8 vs 56.0 years) and representation of Black patients was significantly higher in RWE than RCT studies (25.3% vs 2.9%), both P&lt; .001. Mean age at metastatic diagnosis in SEER was 59.0 years; age at 1L initiation was not reported. SEER included 13.4% Non-Hispanic Black patients. Hispanic representation was 11.2% in RWE, not reported in RCT, and 15.9% in SEER studies (Table). Conclusions: Decisions about treatment choices among clinicians and payers are primarily driven by RCT results, yet they may not be representative of real-world populations. We found that RCTs had lower representation of older and Black patients than both SEER and RWE studies. Limitations included varying study periods, lack of Hispanic ethnicity reporting in RCTs, differential SEER participation by US region, and potential patient overlap. Well-conducted RWE studies may fill gaps left by RCTs for improving representation and generalizability to patients with metastatic breast cancer. [Table: see text]
Telemonitoring program for genito-urinary cancer patients treated with oral anticancer agents.
Authors: Lorene Seguin, Melanie Garcia, Morgane Dulac, Frederic Benizri, Cecile Vicier, Mathilde Guerin, Marie France Muscat, Audrey Monneur, Gwenaelle Gravis
Journal: Journal of Clinical Oncology (2023)

e18731 Background: Oral anticancer agents (OAA) used has dramatically increased in treating genito-urinary (GU) cancer. Patients with metastatic prostate and kidney cancers, have advanced age, with comorbidities. The risks of OAA for this population with adverse effects, drug interactions and ambulatory administration must be detected, prevented and managed to decrease toxicity, improve compliance and efficacy. Here, we report the data of our comprehensive cancer center telemonitoring program named Outside the walls of the hospital (OWH), combining medical oncologist coordination, clinical pharmacist (CP) evaluations, and nurse follow-ups. Methods: Data from patients treated with OAA for advanced and metastatic prostate or kidney cancers in our center during year 2022 were retrospectively evaluated. At the start of OAA, the patients benefit from a consultation with the oncologist, clinical nurse (CN), and CP. For each drug, a standard telemonitoring program has been planned according to the patient's age and comorbidities. Results: The mean age of the patients was 68 years (44-90), 42% of the patients were over 70 years, 84% were men and 96% were in a metastatic setting. Out of 347 GU patients, 118 were included in the OWH telemonitoring program in 2022, representing 14% of the whole cancers patients enrolled in this program. Of these 118 new GU patients, 80% had a CP consultation, 76% for next generation hormonal therapy (NGHT) for advanced or metastatic prostate cancer and 24% for tyrosine kinase inhibitors (TKI) for kidney cancer. At least one drug interactions was detected for 54% of patients (61% of the NGHT and 35% of TKI). The associations was strongly discouraged for 18% because of an increase or decrease in drug concentration requiring a switch or an adaptation of dosage at the outset (statin (11 patients), oral anticoagulant (5 patients), analgesic (1 patient)). At least 1 complementary alternative medicine was used by 29% with 55% of them had an interaction with OAA. During follow-up, the frequency of consultations with CN or physician is reduced over time, in order to give priority to telemonitoring and visits to the oncologist for tumor assessment and if necessary at the request of the nurse or the patient. Conclusions: The OWH program makes it possible to limit medical visits by ensuring safe monitoring. It promotes patient empowerment and allows for medical visits when necessary, in the current context of declining medical demographic for an often elderly and fragile population.
Real-world effectiveness of prophylactic tixagevimab-cilgavimab monoclonal antibodies on incidence and severity of COVID-19 infection in patients with cancer.
Authors: Maryam Naser, Prarthna V Bhardwaj, Fatima Zahid Warriach, Yamna Jadoon, Kush Gupta, Vida Rastegar, Chandravathi Loke, Sudeep Kumar Siddappa Malleshappa
Journal: Journal of Clinical Oncology (2023)

e18843 Background: Mortality rate secondary to COVID-19 in patients with cancer is estimated to be &gt; 10% after vaccination, with an increased risk of infection and hospitalization The FDA granted emergency use approval for pre-exposure prophylaxis with tixagevimab-cilgavimab (Evusheld)based on preliminary results from the PROVENT trial conducted before the emergence of the Omicron variant. However, there are limited real-world studies investigating the impact of Evusheld on COVID-19 in patients with cancer, especially after Omicron became the most common circulating variant in the US in Nov 2021. We assessed the impact of Evusheld on the incidence and severity of COVID-19 at our institution. Methods: We conducted a retrospective descriptive study in our institution on patients with cancer who received Evusheld between Dec 2021 and Mar 2022 with a 6 month follow-up. Primary outcome was incidence of COVID-19. Secondary outcomes included rate of hospitalization related to COVID-19 and associated mortality. Results: Of the 228 patients included in this study, 90% were White with a median age of 67 years, 67% had a hematologic malignancy, 98% were vaccinated against COVID-19, and 72.8% received the recommended 300mg dosing during the study period. Thirty-one patients (13.6%) developed COVID-19, with an average time to diagnosis of 43 days from receiving Evusheld, of whom 26 (83%) were symptomatic. Infected patients were of an average age of 60 years with a BMI of 26, and only a minority (3.2%) had prior COVID-19. Most had hematologic malignancies (77.4%), with the most common being non-Hodgkin lymphoma. Most were receiving chemotherapy (68%) at the time of diagnosis. Third of the affected patients received ani-CD20 treatment (32%). Most received only 150 mg dose (80.6%) of Evusheld. 8(33%) patients with hematological malignancy and 3 (42%) with solid malignancy received Paxlovid after diagnosis. All patients who had COVID-19 were previously vaccinated, with the majority receiving 3 doses (64.5%). Five (16%) patients were hospitalized for COVID-19, of whom 4 had hematological malignancy; one with hematological malignancy required mechanical ventilation and died. Conclusions: Overall, the incidence of COVID-19 following Evusheld was higher than in the PROVENT trial. This could be attributed to the ineffectiveness of Evusheld against new variants. Infections appeared to be more common and severe in patients with hematologic malignancies. [Table: see text]
Survival trends among patients with mesothelioma: Impact of initial therapy at academic centers.
Authors: Ariana Mooradian, ErinMarie Kimbrough, Alexander Hochwald, Guilherme Sacchi de Camargo Correia, Rami Manochakian, Yujie Zhao, Yanyan Lou
Journal: Journal of Clinical Oncology (2023)

e20540 Background: Mesothelioma is an aggressive malignancy with few approved treatment options. Rare malignancies are often seen in higher volume at academic centers which are considered equipped with better expertise. Outcomes of mesothelioma in the novel therapeutic era and impact of initial treatment at academic versus community centers have not been reported. Methods: Mesothelioma cases from 2004-2019 were collected from The National Cancer Database (NCDB). Epidemiologic factors including sex, age, income, education, insurance status and location were assessed as well as overall survival across academic and community centers. Overall survival (OS) was plotted by type of treatment facility, accounting for several factors available in NCDB. Results: A total of 30136 mesothelioma patients were included in the analysis. 13482 (44.7%) were treated in academic centers and 16654 (55.3%) were treated in community practice locations. A higher proportion of patients with comorbidity scores of 2 or higher were seen in the community setting as compared to the academic setting (12.2% vs 7.6%). The distribution of diagnostic stages was similar between academic and community settings (14.1% vs 14.5% Stage I; 28.5% vs 30.7% Stage IV). A higher number of patients received surgery (39.6% vs 21.3%), chemotherapy (59% vs 45.3%), and immunotherapy (5.2% vs 3.5%) when presenting to academic rather than community settings, respectively (p value &lt; 0.001). OS for all patients was 1.093 years (range: 0-16.47 years) for those treated in an academic center and 0.66 years (95% CI: 0-16.690; p &lt; 0.001) for those treated in the community. Conclusions: Data from NCDB database shows that treatment of mesothelioma at academic centers was associated with improved overall survival when compared to receiving treatment in the community despite seeing similar proportions of early and late-stage disease at presentation. Patients were more likely to receive treatment of any kind if presenting to academic centers.
Multicenter pharmacokinetic study of pembrolizumab for non-small cell lung cancer in adults aged older than 75 years.
Authors: Yuta Yamanaka, Takayasu Kurata, Kageaki Watanabe, Yukio Hosomi, Hidehito Horinouchi, Yuichiro Ohe, Yoshiro Nakahara, Tetsuhiko Asao, Sho Saeki, Yukari Tsubata, Yu Fujita, Jun Sakakibara-Konishi, Hidenori Mizugaki, Mayu Ouchi, Shigehiro Yagishita, Akinobu Hamada
Journal: Journal of Clinical Oncology (2023)

e21098 Background: Pembrolizumab (Pemb) is a key drug for the treatment of advanced or recurrent non-small cell lung cancer (NSCLC). However, there are limited data on Pemb use in older adults aged &gt; 75 years with NSCLC, especially in terms of pharmacokinetics (PK). Methods: This open-label multicenter observational study aimed to evaluate real-world data on the safety, efficacy, and blood concentrations of Pemb (both monotherapy and combination therapies) in older adults with NSCLC. Blood samples for PK analysis were collected immediately before Pemb administration. Quantitative Pemb concentrations were measured by liquid chromatography-mass spectrometry. Results: We enrolled 100 patients from July 2019 to September 2020; one patient was excluded due to stage migration. Patient characteristics were as follows: median age, 78 (75–87) years; male/female ratio, 70/29; performance status (PS) 0–1/2–3, 85/14; adenocarcinoma/squamous cell carcinoma/others, 62/25/12; stage I–III/IV/postoperative recurrence (TNM 7th edition), 9/60/30; PD-L1 TPS &lt; 1%/1%–49%/≥50%, 12/31/48; and monotherapy/combination therapy, 65/34. The best overall efficacy was CR/PR/SD/PD (7/40/32/20), and the response rate was 47.5%. The median progression-free survival (PFS) and overall survival (OS) were 8.0 and 19.0 months, respectively. The adverse event profile was generally similar to that reported in previous studies. In total, 77 blood samples were collected immediately before the second cycle (C1 trough). Although no clear association between Pemb concentrations and patient background was found, PFS and OS were significantly shortened in the population with low C1 trough, a population characterized by lower PS, high number of metastatic organs at the beginning of treatment, and low blood albumin level. Conclusions: In older adults aged &gt; 75 years with NSCLC and low albumin levels and PS and a high number of metastatic organs, C1 trough of Pemb is reduced and not expected to prolong PFS and OS. Clinical trial information: UMIN000036606 .
A case-control study of 10,757 individuals to assess potentially modifiable risk factors, including stress, for breast cancer among Chinese patients in Hong Kong.
Authors: Winnie Yeo, Lok-Wa Yuen, Kelvin Kf Tsoi, Emily YY Chan, Carol Kwok, Sung Inda Soong, Ting Y. Ng, Joanne Chiu, Miranda Chan, Sharon Wing Wai Chan, Ting T. Wong, Yolanda HY Chan, Lawrence PK Li, Chun C Yau, Wai K. Hung, Polly Suk-yee Cheung
Journal: Journal of Clinical Oncology (2023)

e22522 Background: Breast cancer is the most common cancer in women worldwide. Both intrinsic and environmental factors contribute to the disparities in breast cancer incidence across different regions. In Hong Kong, the incidence has been increasing in the past decades. With over 4700 women diagnosed in 2019, breast cancer is responsible for 27% of all female cancers in Hong Kong. Apart from intrinsic non-modifiable risk factors, some risk factors are modifiable and may reduce cancer risk. Methods: We conducted a case-control study that involved breast cancer patients from the Hong Kong Breast Cancer Registry with matched healthy controls from the community between 2014 and 2017. A standardized written questionnaire was used through face-to-face interviews of all study participants. The questionnaire collected information on participants’ demographics, general health, smoking history and other lifestyle factors including physical activity, self-assessed dietary habits (balanced, vegetarian, meat and dairy-rich diets), self-perceived stress levels (measured with a 4-point Likert scale, and high stress level was defined as having over 50% of the participant’s time with stress being scored 3 or above out of a Likert scale of 4), body mass index, family history, menstrual and reproductive history, and history on the use of oral contraceptives and hormone replacement therapy. Multiple logistic regression was fitted to compare all risk factors. Results: A total of 5,186 breast cancer patients and 5,571 controls were recruited. Modifiable risk factors that were shown to be associated with an increased risk of breast cancer included self-perceived high stress level (adjusted odd ratios [aOR] = 3.44; 95% CI = 3.13-3.78), meat-rich diet (aOR = 1.77; 95% CI = 1.54-2.04), dairy-rich diet (aOR = 3.33; 95% CI = 2.01-5.52), overweight/obese status (aOR = 1.21; 95% CI = 1.10-1.32), delayed child-bearing (aOR = 2.23; 95% CI = 1.79-2.79), nulliparity (aOR = 1.21; 95% CI = 1.08-1.35) and ever use of oral contraceptives (aOR = 1.34; 95% CI = 1.22-1.47), while exercise (OR = 0.62; 95% CI = 0.56-0.68) and breast-feeding (aOR = 0.76; 95% CI = 0.69-0.83) were associated with reduced risk. Conclusions: In Hong Kong, high stress level, meat- and dairy- rich diet, overweight/obese, reproductive history and use of oral contraceptives were identified to be modifiable risk factors for breast cancer. Adjusting these factors through lifestyle modification may curb the increasing trend of breast cancer incidences in the coming decades.